Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys

Edward S Schelegle, Lisa Miller, Laurel J Gershwin, Michelle V. Fanucchi, Laura S. Van Winkle, Joan E. Gerriets, William F. Walby, Valerie Mitchell, Brian K. Tarkington, Viviana J. Wong, Gregory L. Baker, Lorraine M. Pantle, Jesse P. Joad, Kent E Pinkerton, Reen Wu, Michael J. Evans, Dallas M. Hyde, Charles Plopper

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Abstract

Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.

Original languageEnglish (US)
Pages (from-to)74-85
Number of pages12
JournalToxicology and Applied Pharmacology
Volume191
Issue number1
DOIs
StatePublished - Aug 15 2003

Fingerprint

Dermatophagoides Antigens
Ozone
Aerosols
Macaca mulatta
Allergens
Inhalation
Haplorhini
Air
Airway Resistance
Eosinophilia
Immunoglobulin E
Histamine
Serum
Dermatophagoides farinae
Allergies
Bronchioles
Bordetella pertussis
Intraperitoneal Injections
Eosinophils
Hypersensitivity

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys. / Schelegle, Edward S; Miller, Lisa; Gershwin, Laurel J; Fanucchi, Michelle V.; Van Winkle, Laura S.; Gerriets, Joan E.; Walby, William F.; Mitchell, Valerie; Tarkington, Brian K.; Wong, Viviana J.; Baker, Gregory L.; Pantle, Lorraine M.; Joad, Jesse P.; Pinkerton, Kent E; Wu, Reen; Evans, Michael J.; Hyde, Dallas M.; Plopper, Charles.

In: Toxicology and Applied Pharmacology, Vol. 191, No. 1, 15.08.2003, p. 74-85.

Research output: Contribution to journalArticle

Schelegle, Edward S ; Miller, Lisa ; Gershwin, Laurel J ; Fanucchi, Michelle V. ; Van Winkle, Laura S. ; Gerriets, Joan E. ; Walby, William F. ; Mitchell, Valerie ; Tarkington, Brian K. ; Wong, Viviana J. ; Baker, Gregory L. ; Pantle, Lorraine M. ; Joad, Jesse P. ; Pinkerton, Kent E ; Wu, Reen ; Evans, Michael J. ; Hyde, Dallas M. ; Plopper, Charles. / Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys. In: Toxicology and Applied Pharmacology. 2003 ; Vol. 191, No. 1. pp. 74-85.
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abstract = "Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.",
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